Rapid and accurate measurement of biological and chemical analytes is important in many fields, ranging from diagnostics, to industrial process control, to environmental monitoring, to scientific research. Chemically sensitive, and in particular, ion-sensitive field effect transistors (“chemFETs” and “ISFETs” respectively) have been used for such measurements for many years, e.g. Bergveld, Sensors and Actuators, 88: 1-20 (2003); Yuqing et al., Biotechnology Advances, 21: 527-534 (2003); and the like. More recently, attempts have been made to fabricate arrays of such sensors using integrated circuit technologies to obtain spatially distributed and multi-analyte measurements using a single device, e.g., Yeow et al., Sensors and Actuators B 44: 434-440 (1997); Martinoia et al., Biosensors & Bioelectronics, 16: 1043-1050 (2001); Milgrew et al., Sensors and Actuators B 103: 37-42 (2004); Milgrew et al., Sensors and Actuators B, 111-112: 347-353 (2005); Hizawa et al., Sensors and Actuators B, 117: 509-515 (2006); Heer et al., Biosensors and Bioelectronics, 22: 2546-2553 (2007); and the like. Such efforts face several difficult technical challenges, particularly when ISFET sensor arrays have scales in excess of thousands of sensor elements and densities in excess of many hundreds of sensor elements per mm2 Such challenges include making large-scale arrays with sensor elements having uniform performance characteristics from sensor to sensor within the array, and making sensor elements with footprints on the order of microns which are capable of generating signals detectable against a background of many noise sources from both the sensor array itself and a fluidics system that conveys reactants or analyte-containing samples to the array, For ISFET arrays comprising sensor elements with charge-sensitive components, such as floating gates, the former challenge is exacerbated by the accumulation of trapped charge in or adjacent to such components, which is a common side product of semiconductor fabrication technologies. The latter challenge is exacerbated by the requirement that analytes of interest directly or indirectly generate a charged species that accumulates at or on a charge-sensitive component of the ISFET sensor. In very dense arrays, diffusion, reactivity of the analyte or its surrogate, cross-contamination from adjacent sensors, as well as electrical noise in the sample fluid can all adversely affect measurements. The availability of large-scale ISFET array that overcome these challenges would be highly useful in the above fields, particularly where ever highly parallel multiplex chemical measurements are required, such as in the large scale genetic analysis of genomes.